The brain makes its own Valium: Built-in seizure brake?

The very fact that a drug has a mind-altering effect is a strong clue that sitting somewhere on the surfaces of brain-situated nerve cells of one type or another are proteins that seem on first glance to have been made for the purpose of driving the cells on which they sit into a frenzy or a stupor when molecules of one or another specific drug bind to them.

In fact, these drug-responsive surface proteins turn out to be receptors for substances produced within our own brains, invariably for very good reasons. A study just reported in the journal NEURON suggests the probable explanation for the action of so-called benzodiazepines – a drug class that includes such famous brand names as the anti-anxiety compound Valium and the sleeping pill Halcion.

Stanford neurologist John Huguenard, PhD, has conducted several pathbreaking experiments in the past few years highlighting the seizure-inducing capacity of the thalamus, a deep-brain structure that acts as a combined relay station and resonance chamber, both shaping sensory inputs for distribution to various higher-level centers in the cerebral cortex and generating rhythms associated with sleep. Too much of the wrong kind of stimulation – or not enough of the right kind of inhibition – can cause the thalamic rhythms to get too dramatic, triggering seizures.

Now, in its most recent set of findings, his lab has shown that very specific nerve-cell clusters in the rodent thalamus (and presumably in the human one, too) secrete a protein that lands on precisely the same thalamic nerve-cell receptors, and induces precisely the same activity on the part of those receptors, that Valium does – and that it counters the thalamus’s aberrant tendency to initiate seizures in susceptible animals or people.

In addition to its archetypical sedative role, Valium, or diazepam, was among the earliest drug treatments for epilepsy. Now we know why. (Valium has long been superseded by other more-effective and safer drugs for treating epilepsy.)

This is by no means the first time an internally produced substance has been fingered as being the bone fide designated activator or inhibitor of a certain kind of brain activity – tasks for which psychoactive drugs are mere mimics (and pretty sloppy, often addictive ones at that). As I wrote in my press release on this study, the past several decades have seen a series of such discoveries:

In 1974, [internally produced] proteins called endorphins, with biochemical activity and painkilling properties similar to that of opiates, were isolated. A more recently identified set of substances, the endocannabinoids, mimic the memory-, appetite- and analgesia-regulating actions of the psychoactive components of cannabis, or marijuana.

Kind of makes me feel like writing a book about the brain as a pulsing, gurgling drug factory. I know what I’m going to call it: “Sulcus of the Dolls.”